Identification of a Novel Response Regulator, Crr1, That Is Required for Hydrogen Peroxide Resistance in Candida albicans

Candida albicans colonises numerous niches within humans and thus its success as a pathogen is dependent on its ability to adapt to diverse growth environments within the host. Two component signal transduction is a common mechanism by which bacteria respond to environmental stimuli and, although less common, two component-related pathways have also been characterised in fungi. Here we report the identification and characterisation of a novel two component response regulator protein in C. albicans which we have named CRR1 (Candida Response Regulator 1). Crr1 contains a receiver domain characteristic of response regulator proteins, including the conserved aspartate that receives phosphate from an upstream histidine kinase. Significantly, orthologues of CRR1 are present only in fungi belonging to the Candida CTG clade. Deletion of the C. albicans CRR1 gene, or mutation of the predicted phospho-aspartate, causes increased sensitivity of cells to the oxidising agent hydrogen peroxide. Crr1 is present in both the cytoplasm and nucleus, and this localisation is unaffected by oxidative stress or mutation of the predicted phospho-aspartate. Furthermore, unlike the Ssk1 response regulator, Crr1 is not required for the hydrogen peroxide-induced activation of the Hog1 stress-activated protein kinase pathway, or for the virulence of C. albicans in a mouse model of systemic disease. Taken together, our data suggest that Crr1, a novel response regulator restricted to the Candida CTG clade, regulates the response of C. albicans cells to hydrogen peroxide in a Hog1-independent manner that requires the function of the conserved phospho-aspartate

Carbon and nitrogen cycling in a shallow productive sub-tropical coastal embayment (western Moreton Bay, Australia)

Climatic variables, water quality, benthic fluxes, sediment properties, and infauna were measured six times over an annual cycle in a shallow sub-tropical embayment to characterize carbon and nutrient cycling, and elucidate the role of pelagic–benthic coupling. Organic carbon (OC) inputs to the bay are dominated by phytoplankton (mean 74%), followed by catchment inputs (15%), and benthic microalgae (BMA; 9%). The importance of catchment inputs was highly variable and dependent on antecedent rainfall, with significant storage of allochthonous OC in sediments following high flow events and remineralization of this material supporting productivity during the subsequent period. Outputs were dominated by benthic mineralization (mean 59% of total inputs), followed by pelagic mineralization (16%), burial (1%), and assimilation in macrofaunal biomass (2%). The net ecosystem metabolism (NEM = production minus respiration) varied between −4 and 33% (mean 9%) of total primary production, whereas the productivity/respiration (p/r) ranged between 0.96 and 1.5 (mean 1.13). Up to 100% of the NEM is potentially removed via the demersal detritivore pathway. Dissolved inorganic nitrogen (DIN) inputs from the catchment contributed less than 1% of the total phytoplankton demand, implicating internal DIN recycling (pelagic 23% and benthic 19%) and potentially benthic dissolved organic nitrogen (DON) fluxes (27%) or N fixation (up to 47%) as important processes sustaining productivity. Although phytoplankton dominated OC inputs in this system, BMA exerted strong seasonal controls over benthic DIN fluxes, limiting pelagic productivity when mixing/photic depth approached 1.3. The results of this study suggest low DIN:TOC and net autotrophic NEM may be a significant feature of shallow sub-tropical systems where the mixing/photic depth is consistently less than 4